Structural Systems Pharmacology: A New Frontier in Discovering Novel Drug Targets
| Autor: | Lei Xie, Xiaoxia Ge, Hepan Tan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Drug
Chemistry Pharmaceutical media_common.quotation_subject Systems biology Clinical Biochemistry Structural system Biophysics Drug Resistance Druggability Pharmacology Biology Drug Discovery Humans Molecular Targeted Therapy media_common Genome Human Drug discovery Systems Biology Computational Biology Phenotype Pharmaceutical Preparations Cheminformatics Drug Design Molecular targets Molecular Medicine Identification (biology) |
| Zdroj: | Current Drug Targets. 14:952-958 |
| ISSN: | 1389-4501 |
| DOI: | 10.2174/1389450111314090003 |
| Popis: | The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|